Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Odd Biochemistry Yields Lethal Bacterial Protein

Published: Wednesday, January 23, 2013
Last Updated: Wednesday, January 23, 2013
Bookmark and Share
While working out the structure of a cell-killing protein produced by some strains of the bacterium Enterococcus faecalis, researchers stumbled on a bit of unusual biochemistry.

They found that a single enzyme helps form distinctly different, three-dimensional ring structures in the protein, one of which had never been observed before.

The new findings, reported in Nature Chemical Biology, should help scientists find new ways to target the enterococcal cytolysin protein, a “virulence factor that is associated with acute infection in humans,” said University of Illinois chemistry and Institute for Genomic Biology professor Wilfred van der Donk, who conducted the study with graduate student Weixin Tang.

Enterococcus faecalis (EN-ter-oh-cock-us faye-KAY-liss) is a normal microbial inhabitant of the gastrointestinal tracts of humans and other mammals and generally does not harm its host. Some virulent strains, however, produce cytolysin (sigh-toe-LIE-sin), a protein that, once assembled, attacks other microbes and kills mammalian cells.

“The cytolysin protein made by Enterococcus faecalis consists of two compounds that have no activity by themselves but when combined kill human cells,” van der Donk said. “We know from epidemiological studies that if you are infected with a strain of E. faecalis that has the genes to make cytolysin, you have a significantly higher chance of dying from your infection.” E. faecalis contributes to root canal infections, urinary tract infections, endocarditis, meningitis, bacteremia and other infections.

Enterococcal cytolysin belongs to a class of antibiotic proteins, called lantibiotics, which have two or more sulfur-containing ring structures. Scientists had been unable to determine the three-dimensional structure of this cytolysin because the bacterium produces it at very low concentrations. Another problem that has stymied researchers is that the two protein components of cytolysin tend to clump together when put in a lab dish.

Van der Donk and Tang got around these problems by producing the two cytolysin components separately in another bacterium, Escherichia coli (esh-uh-REE-kee-uh KOH-lie), and analyzing them separately.

“The two components are both cyclic peptides, one with three rings and the other with two rings,” van der Donk said. “Curiously, a single enzyme makes both compounds.”

In a series of experiments, the researchers found that one ring on each of the proteins adopted a (D-L) stereochemistry that is common in lantibiotics (see image, above). But the other rings all had an unusual (L-L) configuration, something van der Donk had never seen before.

Scientists had assumed that the enzyme that shaped enterococcal cytolysin, a lantibiotic synthetase, acted like a three-dimensional mold that gave the ring structures of cytolysin the exact same stereochemistry, van der Donk said.

“But we found that the enzyme, enterococcal cytolysin synthetase, makes the rings with different stereochemistry,” he said. “I don’t know of any other examples where one enzyme can make very similar products but with different stereochemistries.”

The researchers don’t know how the enzyme accomplishes this feat, but found a clue in the sequence of amino acids that make up the protein rings. The chemical characteristics of the three amino acids in the middle of the ring structure and their proximity to another amino acid, a cysteine, determined whether the rings took on a D-L or L-L stereochemistry.

The researchers tested the idea that the amino acid sequence of the cytolysin protein was guiding the stereochemistry by looking at other lantibiotic proteins with similar sequences. So far, every protein they’ve tested that has the same sequence characteristics conforms to the pattern they discovered, van der Donk said.

Further tests showed that the cytolysin produced in E. coli had the same anti-microbial and cell-killing potency as the E. faecalis variety.

“Knowing the structure of enterococcal cytolysin and having a method to produce it in relatively large quantities will allow scientists to find out how it kills human cells and, in turn, how we might fight against it,” van der Donk said.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Epigenetic Switches that turn Stem Cells into Blood Vessel Cells Uncovered
Researchers at the University of Illinois have identified a molecular mechanism that directs embryonic stem cells to mature into endothelial cells.
Monday, June 29, 2015
Carbon Nanoparticles you can Make at Home
Researchers have found an easy way to produce carbon nanoparticles that are small enough to evade the body’s immune system, reflect light in the near-infrared range for easy detection, and carry payloads of pharmaceutical drugs to targeted tissues.
Friday, June 19, 2015
Crop-rotation Resistant Rootworms Have A Lot Going on in Their Guts
After decades of effort, scientists are finally figuring out how insects develop resistance to environmentally friendly farming practices – such as crop rotation – that are designed to kill them.
Thursday, June 11, 2015
How TALENs Find Their Way Around the Genome
Scientists from the University of Illinois Urbana-Champaign have discovered how a genome editing technology finds its way to a specific location in the genome.
Thursday, June 04, 2015
Epigenetic Hangover
New research hints at the long term effects of teenage binge drinking on a genetic level.
Tuesday, May 26, 2015
Surveys Miss Majority Of Poisonings, Underestimate Cost By Billions
Health surveys may underestimate the number of poisonings in the United States by 60 percent to 90 percent, according to a report in the journal Clinical Toxicology by University of Illinois at Chicago researchers.
Wednesday, April 15, 2015
Molecule-making Machine Simplifies Complex Chemistry
Chemists built the machine to assemble complex small molecules at the click of a mouse.
Thursday, March 19, 2015
Microtubes Create Cozy Space For Neurons To Grow
Illinois researchers developed a platform to grow and study neuron cells using tiny rolled microtubes.
Friday, November 14, 2014
Some Plants Regenerate by Duplicating their DNA
A plant’s ability to duplicate its genome within individual cells influences its ability to regenerate.
Thursday, November 13, 2014
Team Discovers How Microbes Build a Powerful Antibiotic
Researchers discovery opens up new avenues of research into thousands of similar molecules.
Wednesday, October 29, 2014
Banked Blood Grows Stiffer With Age
It may look like fresh blood and flow like fresh blood, but the longer blood is stored, the less it can carry oxygen into the tiny microcapillaries of the body.
Monday, September 08, 2014
New Material Could Enhance Fast and Accurate DNA Sequencing
Nanopores in the material MoS2 sequence DNA more accurately, quickly and inexpensively.
Tuesday, August 19, 2014
Researchers See Stem Cells Take Initial Step Toward Development
Study represents the first time this critical step has been demonstrated in a laboratory.
Tuesday, June 03, 2014
Combining Weak Chemical Forces to Strengthen a Novel Imaging Technology
Illinois researchers turn current contrast agent technology on its head—or rather, they turn it inside out.
Thursday, May 22, 2014
It Takes A(n Academic) Village to Determine an Enzyme's Function
Scientists have sequenced the genomes of nearly 6,900 organisms, but they know the functions of only about half of the protein-coding genes thus far discovered.
Wednesday, October 02, 2013
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
Experimental MERS Vaccine Shows Promise in Animal Studies
A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines.
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
Understanding the Molecular Origin of Epigenetic Markers
Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
Diagnostic Test Developed for Enterovirus D68
researchers at Washington University School of Medicine in St. Louis have developed a diagnostic test to quickly detect enterovirus D68 (EV-D68), a respiratory virus that caused unusually severe illness in children last year.
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
Sweet Revenge Against Superbugs
A special type of synthetic sugar could be the latest weapon in the fight against superbugs.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!